Pacific Pharma


AA Medical
Full Prescribing Info
Each film coated tablet contains Rosuvastatin Calcium Eq. to Rosuvastatin 5 mg, 10 mg or 20 mg.
Excipients/Inactive Ingredients: 10 mg & 20 mg tablet: Color: Red oxide of Iron (ROSUVAPAC 10), Lake Quinoline Yellow WS (ROSUVAPAC 20) & Titanium Dioxide.
Pharmacotherapeutic Group: HMG-CoA reductase inhibitors. ATC code: C10AA07.
Pharmacology: Pharmacodynamics: Mechanism of action: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering.
Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
Pharmacokinetics: Absorption: Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours after oral administration. The absolute bioavailability is approximately 20%.
Distribution: Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin.
Metabolism: Rosuvastatin undergoes limited metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for cytochrome P450-based metabolism. CYP2C9 was the principal isoenzyme involved, with 2C19, 3A4 and 2D6 involved to a lesser extent. The main metabolites identified are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin whereas the lactone form is considered clinically inactive. Rosuvastatin accounts for greater than 90% of the circulating HMG-CoA reductase inhibitor activity.
Excretion: Approximately 90% of the rosuvastatin dose is excreted unchanged in the faeces (consisting of absorbed and nonabsorbed active substance) and the remaining part is excreted in urine. Approximately 5% is excreted unchanged in urine. The plasma elimination half-life is approximately 19 hours. The elimination half-life does not increase at higher doses. The geometric mean plasma clearance is approximately 50 litres/hour (coefficient of variation 21.7%).
Treatment of hypercholesterolaemia: Adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) or mixed dyslipidaemia (type IIb) as an adjunct to diet when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate. Homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.
5 mg tablet: Prevention of Cardiovascular Events: Prevention of major cardiovascular events in patients who are estimated to have a high risk for a first cardiovascular event, as an adjunct correction of other risk factors.
Dosage/Direction for Use
Before treatment initiation the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines. Rosuvastatin may be given at any time of day, with or without food.
Treatment of hypercholesterolaemia: The recommended start dose is 5 mg or 10 mg orally once daily in both statin naïve or patients switched from another HMG CoA reductase inhibitor. The choice of start dose should take into account the individual patient's cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions. A dose adjustment to the next dose level can be made after 4 weeks, if necessary. In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses (see Side Effects), a final titration to the maximum dose of 40 mg should only be considered in patients with severe hypercholesterolaemia at high cardiovascular risk (in particular those with familial hypercholesterolaemia), who do not achieve their treatment goal on 20 mg, and in whom routine follow-up will be performed. Specialist supervision is recommended when the 40 mg dose is initiated.
Prevention of cardiovascular events: In the cardiovascular events risk reduction study, the dose used was 20mg daily.
Paediatric population: Paediatric use should only be carried out by specialists. Children and adolescents 10 to 17 years of age (boys Tanner Stage II and above, and girls who are at least 1 year post-menarche). In children and adolescents with heterozygous familial hypercholesterolaemia the usual start dose is 5 mg daily. The usual dose range is 5-20 mg orally once daily.
Titration should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations (see Precautions). Children and adolescents should be placed on standard cholesterol-lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastation treatment. Safety and efficacy of doses greater than 20 mg have not been studied in this population. The 40 mg tablet is not suitable for use in paediatric patients.
Children younger than 10 years: Experience in children younger than 10 years is limited to a small number of children (aged between 8 and 10 years) with homozygous familial hypercholesterolaemia. Therefore, Rosuvastatin is not recommended for use in children younger than 10 years.
Use in the elderly: A start dose of 5mg is recommended in patients > 70 years. No other dose adjustment is necessary in relation to age.
Dosage in patients with renal insufficiency: No dose adjustment is necessary in patients with mild to moderate renal impairment. The recommended start dose is 5 mg in patients with moderate renal impairment (creatinine clearance of <60 ml/min). The 40mg dose is contraindicated in patients with moderate renal impairment. The use of Rosuvastatin in patients with severe renal impairment is contraindicated for all doses.
Dosage in patients with hepatic impairment: There is no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below. However, increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9. In these patients an assessment of renal function should be considered. There is no experience in subjects with Child-Pugh scores above 9. Rosuvastatin is contraindicated in patients with active liver disease.
Race: Increased systemic exposure has been seen in Asian subjects. The recommended start dose in 5mg for patients of Asian ancestry.
The 40 mg dose is contraindicated in these patients.
Dosage in patients with pre-disposing factors to myopathy: The recommended start dose is 5mg in patients with predisposing factors to myopathy. The 40 mg dose is contraindicated in some of these patients.
Route of Administration: By oral route.
10 mg & 20 mg tablet: There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Liver function and CK levels should be monitored. Haemodialysis is unlikely to be of benefit.
10 mg & 20 mg tablet: ROSUVAPAC is contraindicated: in patients with hypersensitivity to rosuvastatin or to any of the excipients; in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN); in patients with severe renal impairment (creatinine clearance <30 mL/min); in patients with myopathy; in patients receiving concomitant ciclosporin.
Special Precautions
10 mg & 20 mg tablet: Renal Effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Rosuvastatin, in particular 40 mg, where it was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease. The reporting rate for serious renal events in post-marketing use is higher at the 40 mg dose. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.
Skeletal Muscle Effects: Effects on skeletal muscle e.g. myalgia, myopathy and rarely, rhabdomyolysis have been reported in Rosuvastatin-treated patients with all doses and in particular with doses > 20 mg. Very rare cases of rhabdomyolysis have been reported with the use of ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction cannot be excluded and caution should be exercised with their combined use.
As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis associated with Rosuvapac in post-marketing use is higher at the 40 mg dose.
Creatine Kinase Measurement: Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result. If CK levels are significantly elevated at baseline (>5xULN) a confirmatory test should be carried out within 5-7 days. If the repeat test confirms a baseline CK >5xULN, treatment should not be started.
Side Effects
10 mg & 20 mg tablet: The adverse events seen with Rosuvapac are generally mild and transient. In controlled clinical trials, less than 4% of Rosuvastatin-treated patients were withdrawn due to adverse events.
Immune system disorders: Rare: hypersensitivity reactions including angioedema.
Nervous system disorders: Common: headache, dizziness.
Gastrointestinal disorders: Common: constipation, nausea, abdominal pain. Rare: pancreatitis.
Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash and urticaria.
Musculoskeletal, connective tissue and bone disorders: Common: myalgia. Rare: myopathy (including myositis) and rhabdomyolysis.
General disorders: Common: asthenia.
5 mg tablet: Store below 30°C. Store in the original package in order to protect from moisture.
10 mg & 20 mg tablet: Store below 30°C in a dry place. Protect from light.
MIMS Class
Dyslipidaemic Agents
ATC Classification
C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
FC tab 5 mg x 3 x 10's. 10 mg x 3 x 10's. 20 mg x 3 x 10's.
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